Reduced urinary kallikrein in hypertensive diabetic patients

Abstract

Renal kallikrein, an enzyme of the distal tubule acting on renal vasodilation through kinin liberation, may participate in the control of renal circulation and blood pressure. To study if impairment of kallikrein secretion can occur in diabetes, 40 nonhypertensive and 29 hypertensive diabetic patients were compared to 30 nondiabetic, nonhypertensive controls. Urinary kallikrein activity (UKA) was measured by its kininogenase activity. Preincubations with trypsin were performed to measure total kallikrein. Compared to UKA in controls [86 ± 9 μg lysylbradykinin (LBK, mean ± SEM) produced per minute of incubation], UKA was significantly reduced in both nonhypertensive (59 ± 8 μg LBK. min −1; p < 0.05) and hypertensive diabetics (26 ± 6 μg LBK. min −1; p < 0.001). The ratio of total/active urinary kallikrein was similar in diabetics and controls. From a multiple stepwise linear regression analysis, the prognostic independent variables for a reduced UKA in diabetic patients were creatinine clearance (Fisher's index: 34.64) and mean blood pressure (Fisher's index: 13.50). These results support the assumption that alterations of renal kallikrein release are associated with renal dysfunction and increased blood pressure in diabetic subjects.